title: Identification of dAven, a Drosophila melanogaster ortholog of the cell cycle regulator Aven.
abstract: Aven is a regulator of the DNA-damage response and G2/M cell cycle progression. Overexpression of Aven is associated with poor prognosis in patients with childhood acute lymphoblastic leukemia and acute myeloid leukemia, and altered intracellular Aven distribution is associated with inﬁltrating ductal carcinoma and papillary carcinoma breast cancer subtypes. Although Aven orthologs have been identified in most vertebrate species, no Aven gene has been reported in invertebrates. Here, we describe a Drosophila melanogaster open reading frame (ORF) that shares sequence and functional similarities with vertebrate Aven genes. The protein encoded by this ORF, which we named dAven, contains several domains that are highly conserved among Aven proteins of fish, amphibian, bird and mammalian origins. In flies, knockdown of dAven by RNA interference (RNAi) resulted in lethality when its expression was reduced either ubiquitously or in fat cells using Gal4 drivers. Animals undergoing moderate dAven knockdown in the fat body had smaller fat cells displaying condensed chromosomes and increased levels of the mitotic marker phosphorylated histone H3 (PHH3), suggesting that dAven was required for normal cell cycle progression in this tissue. Remarkably, expression of dAven in Xenopus egg extracts resulted in G2/M arrest that was comparable to that caused by human Aven. Taken together, these results suggest that, like its vertebrate counterparts, dAven plays a role in cell cycle regulation. Drosophila could be an excellent model for studying the function of Aven and identifying cellular factors that influence its activity, revealing information that may be relevant to human disease.
authors.affiliation: Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Sige
authors.initials: S
authors.lastname: Zou
authors.forename: Joy
authors.initials: J
authors.lastname: Chang
authors.forename: Leesa
authors.initials: L
authors.lastname: LaFever
authors.forename: Wangli
authors.initials: W
authors.lastname: Tang
authors.forename: Erika L
authors.initials: EL
authors.lastname: Johnson
authors.forename: Jack
authors.initials: J
authors.lastname: Hu
authors.forename: Ronit
authors.initials: R
authors.lastname: Wilk
authors.forename: Henry M
authors.initials: HM
authors.lastname: Krause
authors.forename: Daniela
authors.initials: D
authors.lastname: Drummond-Barbosa
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Irusta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D016195:G2 Phase; D006657:Histones / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D034622:RNA Interference; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: C412506:AVEN protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C560411:Aven protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D006657:Histones; D008565:Membrane Proteins